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The structural properties of the mesoscopically confined drug and drug–drug and drug–matrix interactions were investigated in model drug-delivery systems prepared from nonfunctionalized and functionalized SBA-15 mesoporous silicate matrices, loaded with different amounts of indomethacin molecules. 1H MAS and 1H–13C CPMAS NMR spectroscopy indicated that only when the concentration of indomethacin within the mesopores becomes sufficiently high (when the mass fraction of indomethacin within the sample exceeds ∼0.15) do hydrogen bonds between the drug molecules become abundant. Nitrogen sorption analysis and comparison of 1H spin–lattice relaxation times in progressively loaded SBA-15 matrices suggested that at low loading concentrations indomethacin forms a layer on the silicate walls of the mesopores and that at moderate or high loading concentrations rigid nanoparticles that extend throughout the entire mesopore cross section are formed. 1H–29Si HETCOR NMR spectra indicated that the interaction between the indomethacin molecules and the silicate surface was moderate to weak. The 1H–13C CPMAS NMR spectrum of indomethacin embedded within the mesopores of SBA-15 closely resembled the spectrum of the bulk amorphous indomethacin and did not allow to draw firm conclusions about the molecular conformation and the packing of the drug molecules within the pores. On the contrary, variable-temperature 1H spin–lattice relaxation measurements showed that the mesoscopically confined indomethacin is significantly different from the bulk amorphous indomethacin. It does not become rubbery, and it exhibits a solid–solid transition at 363 K that is similar to the phase transition of the crystalline indomethacin solvate with tetrahydrofuran. When indomethacin is incorporated into the functionalized SBA-15 matrix, the interactions between the embedded drug molecules and the walls of the matrix are enhanced.

Compounds embedded into mesoporous or even microporous matrices are interesting for many emerging applications, such as novel catalysts, sensors, batteries, hydrogen storage materials or modern drug delivery devices. We report on two unexpected phenomena regarding the structural and dynamic properties of a model drug substance (indomethacin) when confined in mesoscopic matrices. Firstly, we show that the confinement directs the crystallization of the drug into a stable polymorph that is not otherwise formed at all; its relative amount depends on the pore size. This phenomenon is also explained theoretically using a modified classical heterogeneous nucleation theory. Secondly, we demonstrate that--even at relatively low volume fractions--the confined drug forms a condensed phase in a way that obstructs the passage of the pore channels. This may have far-reaching consequences for understanding the mechanisms of drug release from porous matrices.

According to the International Union of Pure and Applied Chemistry (IUPAC), porous materials are classified into three categories: microporous with pore diameters less than 2 nm, mesoporous having pore diameters between 2 and 50 nm, and macroporous with pore sizes larger than 50 nm. Highly ordered mesoporous silicates such as MCM (Mobil Composition of Matter No. 41, 48,...) and SBA (Santa Barbara Amorphous material No. 1, 3, 15,...) have been long recognized as very promising materials with a rich variety of possible applications (1). The various types of MCM and SBA silicates can be distinguished by the number after the acronym. The three most important MCM materials are: MCM-41 (hexagonal), MCM-48 (cubic) and MCM-50 (lamellar). Also a wide variety of SBA materials has been prepared, such as SBA-1 (cubic), SBA-11 (cubic), SBA-12 (3D hexagonal network), SBA-14 (lamellar), SBA-15 (2D hexagonal) and SBA-16 (cubic cage-structured). They show ordered arrangements of channels and cavities of different geometry confined between walls built up from SiO 2 units. Among all numerous applications of mesoporous materials, ranging from separation technology, catalysis, hydrogen Interest in and thereby also development of ordered mesoporous silicates as drug delivery devices have grown immensely over the past few years. On hand selected cases from the literature, the power of such systems as delivery devices has been established. Specifically, it is shown how it is possible to enhance the release kinetics of poorly soluble drugs by embedding them in mesoporous silicates. Further critical factors governing the structure and release of the model drug itraconazole incorporated in an SBA-15 matrix are briefly reviewed. The possibility of functionalizing the surface of mesoporous matrices also under harsher conditions offers a broad platform for the design of stimuli-responsive drug release, including pH responsive systems and systems which respond to the presence of specific ions, reducing agents, magnetic field or UV light, whose efficiency and biocompatibility has been established in vitro.

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